Hydrocinnamic acid is used in the preparation of pharmaceuticals, including protease inhibitors used in the treatment of HIV. Conventionally, hydrocinnamic acid is produced by hydrogenating the unsaturated aromatic carboxylic acid cinnamic acid. Hydrocinnamic acid can then be subjected to additional downstream conversions, most notably chlorination to produce hydrocinnamoyl chloride.
Although useful, this synthesis can suffer various drawbacks. Cinnamic acid is relatively expensive. Cinnamic acid also is typically available in limited quantities.
Prior attempts to produce hydrocinnamic acid using alternative syntheses have been largely unsuccessful. For example, published international application Nos. WO 96/11898 and WO 96/11900 are directed to processes in which cinnamaldehyde is hydrogenated to produce hydrocinnamaldehyde, which in turn is oxidized using a medium containing molecular oxygen to produce hydrocinnamic acid. However, hydrogenation of cinnamaldehyde produces a mixture of products, namely hydrocinnamic alcohol in addition to hydrocinnamaldehyde.
The hydrogenation product mixture which includes both hydrocinnamaldehyde and hydrocinnamic alcohol can be oxidized using molecular oxygen as described in the PCT publications. However, the inventors have found that the resultant oxidation product includes undesirable contamination as result of incomplete oxidation of the hydrocinnamic alcohol. Purifying hydrocinnamic acid requires an additional processing step, which can be difficult, time consuming, and expensive. Further, incomplete oxidation of the hydrogenation mixture results in a loss of yield.